Mimicking Charged Host-Defense Peptides to Tune the Antifungal Activity and Biocompatibility of Amphiphilic Polymers

In this study, we developed a library of 29 amphiphilic polyacrylamides with different charged units, namely, amines, guanidinium, imidazole, and carboxylic acid groups, representative of the natural amino acids lysine, arginine, histidine, and glutamic acid. Ternary polymers incorporating primary ammonium (lysine-like) or imidazole (histidine-like) groups demonstrated superior activity against Candida albicans and biocompatibility with mammalian cells compared to the polymers containing the other charged groups. Furthermore, a combination of primary ammonium, imidazole, and guanidinium (arginine-like) within the same polymer outperformed the antifungal drug amphotericin B in terms of therapeutic index and exhibited fast C. albicans-killing activity. The most promising polymer compositions showed synergistic effects in combination with caspofungin and fluconazole against C. albicans and additionally demonstrated activity against other clinically relevant fungi. Collectively, these results indicate the strong potential of these easily producible polymers to be used as antifungals.PMID:38165721 | DOI:10.1021/acs.biomac.3c01038
Source: Biomacromolecules - Category: Biochemistry Authors: Source Type: research